Breast Surgery, Kansai Medical University Hospital, Osaka, Japan.
Department of Breast Surgery, Kyoto University Hospital, Kyoto, Japan.
Breast. 2018 Apr;38:114-119. doi: 10.1016/j.breast.2017.12.017. Epub 2018 Jan 5.
Adjuvant bisphosphonates lead to better prognosis in postmenopausal breast cancer. However, the association between clinical outcomes and immune modulation by them is still unclear.
In this prospective, open-label phase II study, postmenopausal women with estrogen receptor-positive and human epidermal growth factor receptor 2-negative early-stage breast cancer received neoadjuvant letrozole (LET) for one month, followed by treatment with a single dose of zoledronic acid. The patients underwent an additional 5 months of treatment with LET prior to surgery. The primary endpoint was the tumor objective response rate (ORR) determined by diameter via MRI. The association between the ORR and γδT cell frequencies was assessed as a secondary endpoint.
Out of sixty patients, 55 patients were evaluable for response by MRI. The ORR for LET with zoledronic acid was 38.2% (21/55), which was comparable to that of historical controls (45%). A decrease in the frequency of the Vδ2 T cell subset was observed throughout treatment, and Vδ2 T cells were activated for 6 months. In planned subgroup analyses, patients with low frequencies of Vδ2 T cells prior to zoledronic acid infusion experienced a favorable tumor response compared to those with high frequencies (59.3% [16/27] vs 17.9% [5/28], p = .002). There were no serious adverse events with this treatment regimen.
These results showed that neoadjuvant LET with zoledronic acid could not achieve overall effect for local tumor response. However, patients with a low frequency of γδ T cells would benefit from the treatment including zoledronic acid. (UMIN 000008701).
辅助双膦酸盐可改善绝经后乳腺癌患者的预后。然而，它们与临床结果的关联以及对免疫的调节作用仍不清楚。
在这项前瞻性、开放标签的 II 期研究中，雌激素受体阳性和人表皮生长因子受体 2 阴性的绝经后早期乳腺癌患者接受来曲唑（LET）单月新辅助治疗，然后给予唑来膦酸单次剂量。患者在手术前接受 LET 治疗另外 5 个月。主要终点是通过 MRI 测量的肿瘤客观缓解率（ORR）。次要终点评估了 ORR 与γδT 细胞频率之间的关系。
在 60 名患者中，55 名患者可通过 MRI 评估疗效。LET 联合唑来膦酸的 ORR 为 38.2%（21/55），与历史对照（45%）相当。在整个治疗过程中，Vδ2 T 细胞亚群的频率下降，Vδ2 T 细胞被激活了 6 个月。在计划的亚组分析中，与高频率组相比，唑来膦酸输注前 Vδ2 T 细胞频率较低的患者肿瘤缓解率较好（59.3%[16/27] vs 17.9%[5/28]，p=0.002）。该治疗方案无严重不良事件。
这些结果表明，来曲唑联合唑来膦酸新辅助治疗不能达到局部肿瘤反应的总体效果。然而，γδ T 细胞频率较低的患者将从包括唑来膦酸在内的治疗中获益。（UMIN 000008701）。
